The goals of Dr. Eugene Shapiro, the principal investigator, are: 1) to conduct high quality research to answer important questions about a) the effectiveness of licensed vaccines as they are used in clinical practice and b) the clinical epidemiology and outcomes of patients with Lyme disease, and 2) to mentor young physicians so that they can become successful independent investigators. Dr. Shapiro completed separate fellowships in pediatric infectious diseases and in clinical epidemiology and research methods. He has been on the faculty at the Yale School of Medicine since 1983. During that time he has developed a large network of collaborators at the university, in the community, and throughout the state for his patient-oriented research projects; he also collaborates with the Connecticut Sate Department of Public Health. Because many important questions about vaccines (e.g., the duration of protection or the vaccine's efficacy in subgroups of patients or for specific manifestations of an infection) cannot be answered by randomized clinical trials, Dr. Shapiro has been especially interested in observational (case-control) studies of the efficacy of licensed vaccines. He is particularly well-known for developing methods (and incorporating them into his studies) to minimize bias and to assess the validity of the results of the large-scale case-control studies that he has conducted of the effectiveness of vaccines in clinical practice. If this proposal is funded, it will allow Dr. Shapiro to spend 75% of his time conducting research and serving as a mentor. Dr. Shapiro is currently conducting a case-control study of the clinical effectiveness of varicella vaccine in children. In future years he plans to conduct a case- control study of the effectiveness of the recently-licensed Lyme vaccine and, eventually, a case-control study of the effectiveness of conjugate pneumococcal vaccine (which is expected to be licensed within the next 12-24 months) in children. Dr. Shapiro is also conducting studies of the long-term outcomes of children and adults who were diagnosed as having Lyme disease from 1 to 15 years ago. Dr. Shapiro will serve as a mentor for 1-2 fellows (or young faculty members) each year. The fellows will learn to conduct high-quality clinical studies by working with Clinical Epidemiology Unit. They also will participate in regular research conferences and journal clubs and will meet regularly with Dr. Shapiro to review their progress and to help them develop their own studies as well as to develop strategies for the development of their careers.